PROJECT SUMMARY Difficulties in reciprocal social interaction are hallmark features of several neuropsychiatric disorders, most notably autism spectrum disorder (ASD) and schizophrenia spectrum disorder (SSD)4. While recent studies have demonstrated substantial overlap in genetic etiology between ASD and SSD5-7, little is known about common versus unique neural mechanisms that may underlie these downstream social deficits that cross diagnostic boundaries. Moreover, both ASD and SSD have also been hypothesized as neurometabolic disorders involving excitatory/inhibitory neurotransmitter imbalances8,9, but this hypothesis has not been empirically tested across these groups. Hence, it is hard to draw conclusions about the neural mechanisms underlying shared and distinct deficits in social interaction across ASD and SSD, despite the known genetic overlap between them. Thus, a comprehensive imaging study examining social deficits in youth with ASD and adolescent-onset SSD at the neurochemical, connectivity, as well as functional activation level will be crucial in furthering our understanding of these underlying neural mechanisms. Ultimately, this knowledge could provide key insights into how targeted social skills interventions may impact the organization of large-scale functional brain networks implicated in social cognition in these disorders, leading to improved outcomes. The overall objective of this K99/R00 award is to provide the applicant with additional research training and mentorship to help her achieve her long-term goal of becoming an independent research scientist. Specifically, K99 training goals include: (1) expanding applicants' knowledge about the diagnosis, phenomenology and cognitive neuroscience of adolescent-onset SSD, (2) applying advanced analysis techniques such a dynamic causal modeling to examine interaction of social cognition networks between the two groups, (3) and utilizing magnetic resonance spectroscopy to examine neurometabolic factors underlying social cognition difficulties. While the applicant has strong background in imaging research, the specialized training proposed will further expand her expertise and facilitate transition to a tenure-track faculty position. During the K99 phase, the applicant will be under the primary mentorship of Dr. Carrie Bearden, who will provide research infrastructure, co-ordinate between all other proposed mentors, and ensure that training and study goals are achieved in a timely manner. The proposed mentoring team was selected due to their relevant expertise, history of mentoring young investigators, and commitment to further the applicant's independent career. Results from the K99 phase will be used to generate models about neural mechanisms underlying each group's response to social skills intervention that will be parlayed into the R00 phase. In this phase we will apply an evidence based intervention, examining changes in brain responses following treatment in both ASD and SSD groups. This may help identify and differentiate neural mechanisms modulating treatment effects that may differ in each group, leading to better prediction of treatment response and subsequent long-term maintenance of treatment gains in each group.